Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution.

No abstract

Objectives: To determine the association between frailty and short-term mortality in older adults hospitalized for coronavirus disease 2019 . Design: Retrospective single-center observational study. Setting and participants: Eighty-one patients with COVID-19 confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), at the Geriatrics department of a general hospital in Belgium. Measurements: Frailty was graded according to the Rockwood Clinical Frailty Scale (CFS). Demographic, biochemical, and radiologic variables, comorbidities, symptoms, and treatment were extracted from electronic medical records. Results: Participants (N ¼ 48 women, 59%) had a median age of 85 years (range 65-97 years) and a median CFS score of 7 (range 2-9); 42 (52%) were long-term care residents. Within 6 weeks, 19 patients died. Mortality was significantly but weakly associated with age (Spearman r ¼ 0.241, P ¼ .03) and CFS score (r ¼ 0.282, P ¼ .011), baseline lactate dehydrogenase (LDH; r ¼ 0.301, P ¼ .009), lymphocyte count (r ¼ À0.262, P ¼ .02), and RT-PCR cycle threshold (Ct, r ¼ À0.285, P ¼ .015). Mortality was not associated with long-term care residence, dementia, delirium, or polypharmacy. In multivariable logistic regression analyses, CFS, LDH, and RT-PCR Ct (but not age) remained independently associated with mortality. Both age and frailty had poor specificity to predict survival. A multivariable model combining age, CFS, LDH, and viral load significantly predicted survival. Conclusions and Implications: Although their prognosis is worse, even the oldest and most severely frail patients may benefit from hospitalization for COVID-19, if sufficient resources are available.

The Internet has become an important health information resource for patients and the general public. Wikipedia, a collaboratively written Web-based encyclopedia, has become the dominant online reference work. It is usually among the top results of search engine queries, including when medical information is sought. Since April 2004, editors have formed a group called WikiProject Medicine to coordinate and discuss the English-language Wikipedia’s medical content. This paper, written by members of the WikiProject Medicine, discusses the intricacies, strengths, and weaknesses of Wikipedia as a source of health information and compares it with other medical wikis. Medical professionals, their societies, patient groups, and institutions can help improve Wikipedia’s health-related entries. Several examples of partnerships already show that there is enthusiasm to strengthen Wikipedia’s biomedical content. Given its unique global reach, we believe its possibilities for use as a tool for worldwide health promotion are underestimated. We invite the medical community to join in editing Wikipedia, with the goal of providing people with free access to reliable, understandable, and up-to-date health information.

Sarcopenia is associated with low BMD(a) and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis.

OBJECTIVE To determine the significance of the English Wikipedia as a source of online health information. DESIGN The authors measured Wikipedia's ranking on general Internet search engines by entering keywords from MedlinePlus, NHS Direct Online, and the National Organization of Rare Diseases as queries into search engine optimization software. We assessed whether article quality influenced this ranking. The authors tested whether traffic to Wikipedia coincided with epidemiological trends and news of emerging health concerns, and how it compares to MedlinePlus. MEASUREMENTS Cumulative incidence and average position of Wikipedia compared to other Web sites among the first 20 results on general Internet search engines (Google, Google UK, Yahoo, and MSN, and page view statistics for selected Wikipedia articles and MedlinePlus pages. RESULTS Wikipedia ranked among the first ten results in 71-85% of search engines and keywords tested. Wikipedia surpassed MedlinePlus and NHS Direct Online (except for queries from the latter on Google UK), and ranked higher with quality articles. Wikipedia ranked highest for rare diseases, although its incidence in several categories decreased. Page views increased parallel to the occurrence of 20 seasonal disorders and news of three emerging health concerns. Wikipedia articles were viewed more often than MedlinePlus Topic (p = 0.001) but for MedlinePlus Encyclopedia pages, the trend was not significant (p = 0.07-0.10). CONCLUSIONS Based on its search engine ranking and page view statistics, the English Wikipedia is a prominent source of online health information compared to the other online health information providers studied.

More than 50% of prostate cancers have undergone a genomic reorganization that juxtaposes the androgen-regulated promoter of TMPRSS2 and the protein coding parts of several ETS oncogenes. These gene fusions lead to prostate-specific and androgen-induced ETS expression and are associated with aggressive lesions, poor prognosis, and early-onset prostate cancer. In this study, we showed that an enhancer at 13 kb upstream of the TMPRSS2 transcription start site is crucial for the androgen regulation of the TMPRSS2 gene when tested in bacterial artificial chromosomal vectors. Within this enhancer, we identified the exact androgen receptor binding sequence. This newly identified androgen response element is situated next to two binding sites for the pioneer factor GATA2, which were identified by DNase I footprinting. Both the androgen response element and the GATA-2 binding sites are involved in the enhancer activity. Importantly, a single nucleotide polymorphism (rs8134378) within this androgen response element reduces binding and transactivation by the androgen receptor. The presence of this SNP might have implications on the expression and/or formation levels of TMPRSS2 fusions, because both have been shown to be influenced by androgens.

Androgens increase both the size and strength of skeletal muscle via diverse mechanisms. The aim of this review is to discuss the different cellular targets of androgens in skeletal muscle as well as the respective androgen actions in these cells leading to changes in proliferation, myogenic differentiation, and protein metabolism. Androgens bind and activate a specific nuclear receptor which will directly affect the transcription of target genes. These genes encode muscle-specific transcription factors, enzymes, structural proteins, as well as microRNAs. In addition, anabolic action of androgens is partly established through crosstalk with other signaling molecules such as Akt, myostatin, IGF-I, and Notch. Finally, androgens may also exert non-genomic effects in muscle by increasing Ca(2+) uptake and modulating kinase activities. In conclusion, the anabolic effect of androgens on skeletal muscle is not only explained by activation of the myocyte androgen receptor but is also the combined result of many genomic and non-genomic actions.